The cytochrome P-450 monooxygenases comprise a group of related enzymes which csatalyze the oxidative metabolism of variety of endogenous and exogenous compounds. Differences in the occurrences and properties of the multiple forms of microsomal cytochrome P-450 can affect diverse processes such as carcinogen activiation and detoxificaton, drug clearance, susceptibility to chemical toxins, and hormone metabolism. Work in our laboratory and others has clearly established the occurrence of eight electrophoretic classes, denoted 1, 2, 3a, 3b, 4, 5, and 6, of microsomal cytochrome P-450 in the rabbit. Preliminary evidence presented in this application is suggestive of genetic polymorphism governing the occurrences and structure of P-450 1 and P-450 3b. We propose to characterize the nature and extent of this polymorphism among genetically defined strains of rabbits. The two cytochromes will be isolated and subsequently contrasted by comparative peptide mapping. In addition, monoclonal antibodies will be developed to characterize structural polymorphism and to monitor the occurrence of specific subforms among the genetically defined strains of rabbits. These studies should delineate the nature and extent of the genetic polymorphisms exhibited by this system and provide useful models for the investigation of cytochrome P-450 mediated metabolism and structural aspects of cytochrome P-450 function.